Longitudinal SARS-CoV-2 testing is punctuated by intermittent positivity and variable rates of cycle-threshold decline (preprint)

The COVID-19 pandemic is complicated by cases of vaccine-breakthrough, re-infection, and widespread transmission of variants of concern (VOC). Consequently, the need to interpret longitudinal positive SARS-CoV-2 (SCV-2) tests is crucial in guiding clinical decisions regarding infection control precautions and treatment. Although quantitative tests are not routinely used diagnostically, standard diagnostic RT-PCR tests yield Ct values that are inversely correlated with RNA quantity. In this study, we performed a retrospective review of 72,217 SCV-2 PCR positive tests and identified 264 patients with longitudinal positivity prior to vaccination and VOC circulation. Patients with longitudinal positivity fell into two categories: short-term (207, 78%) or prolonged (57, 22%) positivity, defined as <= 28 (range 1-28, median 16) days and >28 (range 29-152, median 41) days, respectively. In general, Ct values declined over time in both groups; however, 11 short-term positive patients had greater amounts of RNA detected at their terminal test compared to the first positive, and 5 patients had RNA detected at Ct < 35 at least 40 days after initial infection. Oscillating positive and negative results occurred in both groups, although oscillation was seen three times more frequently in prolonged-positive patients. Patients with prolonged positivity had diverse clinical characteristics but were often critically ill and were discharged to high-level care or deceased (22%). Overall, this study demonstrates that caution must be emphasized when interpreting Ct values as a proxy for infectivity, predictor of severity, or a guide for patient care decisions in the absence of additional clinical context.

Molnupiravir, an Oral Antiviral Treatment for COVID-19 (preprint)

BackgroundEasily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.gov NCT04405570). MethodsEligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. ResultsAmong 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. ConclusionsMolnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.